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Biomedical subjects

Hoosen Coovadia

Publications and source records attributed to Hoosen Coovadia.

14 recordsLinked to original sources
PubMed2005

Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomised double-blind placebo-controlled trial.

BACKGROUND: Zinc deficiency is associated with impaired immune function and an increased risk of infection. Supplementation can decrease the incidence of diarrhoea and pneumonia in children in resource-poor countries. However, in children with HIV-1 infection, the safety of zinc supplementation is uncertain. We aimed to assess the role of zinc in HIV-1 replication before mass zinc supplementation is recommended in regions of high HIV-1 prevalence. METHODS: We did a randomised double-blind placebo-controlled equivalence trial of zinc supplementation at Grey's Hospital in Pietermaritzburg, South Africa. 96 children with HIV-1 infection were randomly assigned to receive 10 mg of elemental zinc as sulphate or placebo daily for 6 months. Baseline measurements of plasma HIV-1 viral load and the percentage of CD4+ T lymphocytes were established at two study visits before randomisation, and measurements were repeated 3, 6, and 9 months after the start of supplementation. The primary outcome measure was plasma HIV-1 viral load. Analysis was per protocol. FINDINGS: The mean log(10) HIV-1 viral load was 5.4 (SD 0.61) for the placebo group and 5.4 (SD 0.66) for the zinc-supplemented group 6 months after supplementation began (difference 0.0002, 95% CI -0.27 to 0.27). 3 months after supplementation ended, the corresponding values were 5.5 (SD 0.77) and 5.4 (SD 0.61), a difference of 0.05 (-0.24 to 0.35). The mean percentage of CD4+ T lymphocytes and median haemoglobin concentrations were also similar between the two groups after zinc supplementation. Two deaths occurred in the zinc supplementation group and seven in the placebo group (p=0.1). Children given zinc supplementation were less likely to get watery diarrhoea than those given placebo. Watery diarrhoea was diagnosed at 30 (7.4%) of 407 clinic visits in the zinc-supplemented group versus 65 (14.5%) of 447 visits in the placebo group (p=0.001). INTERPRETATION: Zinc supplementation of HIV-1-infected children does not result in an increase in plasma HIV-1 viral load and could reduce morbidity caused by diarrhoea. RELEVANCE TO PRACTICE: Programmes to enhance zinc intake in deficient populations with a high prevalence of HIV-1 infection can be implemented without concern for adverse effects on HIV-1 replication. In view of the reductions in diarrhoea and pneumonia morbidity, zinc supplementation should be used as adjunct therapy for children with HIV-1 infection.

CD4 Lymphocyte Count↗
PubMed2005

Is there a difference in the efficacy of peripartum antiretroviral regimens in reducing mother-to-child transmission of HIV in Africa?

BACKGROUND: Peripartum antiretroviral regimens have been shown to prevent mother-to-child transmission of HIV (MTCT) in randomized clinical trials; however, direct comparison of published results is impossible given methodological and population differences. OBJECTIVE: To directly compare the efficacy of different antiretroviral regimens in reducing the risk of 6-week MTCT rate in African breastfeeding populations. METHODS: Pooled analysis including all mother-infant pairs from any relevant trial: West African ZDV-placebo trials, Petra ZDV+3TC [two regimens A (pre/intra/post-partum) and B (intra/post-partum), placebo from Uganda and Tanzania], SAINT (NVP and Petra arm B), HIVNET012 (NVP, ultra short ZDV pp) and the Vitamin A trial (as placebo arm in South Africa). Peripartum HIV infection was any positive RNA or DNA polymerase chain reaction test < day 60. The MTCT risk was estimated at 6 weeks for each treatment arm and compared with placebo or single-dose NVP using logistic regression adjusting for maternal CD4 cell count, breastfeeding and birthweight. RESULTS: Overall, 4125 singleton live-births were included; 3629 (88%) were assessed for HIV status at 6 weeks of age. In comparison with placebo, zidovudine + lamivudine (ZDV+3TC) arm A [adjusted odds ratio (AOR), 0.23; P < 0.0001], ZDV+3TC arm B (AOR, 0.49; P < 0.001), antenatal ZDV short (AOR, 0.55; P = 0.006) and nevirapine (NVP) (AOR, 0.60; P = 0.0007) significantly reduced MTCT. In comparison with NVP, only the longest regimen of ZDV+3TC (AOR, 0.39, P < 0.0005) was significantly more effective. CONCLUSION: These results are in line with current World Health Organisation guidelines suggesting equivalence of choice between single-dose NVP and short-course ZDV, and confirm the greater efficacy of ZDV+3TC than with any single antiretroviral drug.

Adult↗
PubMed2005

Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8+ and CD4+ cell responses.

BACKGROUND: The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined. METHODS: HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence. RESULTS: The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus-specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non-Gag proteins were the main target (P=.007). CONCLUSIONS: Gag-specific responses dominate the CD4+ T cell response to HIV, whereas CD8+ T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8+ T cells is associated with enhanced control of viral load.

CD4-Positive T-Lymphocytes↗
PubMed2005

Breast-milk shedding of drug-resistant HIV-1 subtype C in women exposed to single-dose nevirapine.

Single-dose nevirapine reduces intrapartum human immunodeficiency virus 1 type (HIV-1) transmission but may also select for nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance in breast milk (BM) and plasma. Among 32 Zimbabwean women, median 8-week postpartum plasma and BM HIV-1 RNA levels were 4.57 and 2.13 log(10) copies/mL, respectively. BM samples from women with laboratory-diagnosed mastitis (defined as elevated BM Na(+) levels) were 5.4-fold more likely to have HIV-1 RNA levels above the median. BM RT sequences were not obtained for 12 women with BM HIV-1 RNA levels below the lower limit of detection of the assay used. In 20 paired BM and plasma samples, 65% of BM and 50% of plasma RT sequences had NNRTI-resistance mutations, with divergent mutation patterns.

Anti-HIV Agents↗
PubMed2004

Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding: from animal studies to randomized clinical trials.

The major remaining challenge in the prevention of mother-to-child transmission is the reduction of the risk in settings where breast-feeding is common. This review gives an update on ongoing or planned antiretroviral intervention studies in resource-limited settings that are aimed at reducing the risk of mother-to-infant HIV transmission during lactation. These strategies include antiretroviral therapy given to the mother to reduce viral load in plasma and breast milk as well as antiretroviral regimens providing prophylaxis to uninfected infants during the period of breast-feeding. The rationale for the interventions based on animal models and human studies is described as well as the study designs of clinical trials. Potential risks and benefits of these interventions to mothers and infants are also highlighted. Laboratory studies nested within several of these trials will provide a better understanding of the pathogenesis of postnatal HIV transmission and its potential prevention using antiretroviral drugs.

Acquired Immunodeficiency Syndrome↗
PubMed2003

A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1.

To determine the efficacy and safety of 2 inexpensive and easily deliverable antiretroviral (ARV) regimens for the prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) type 1 during labor and delivery, HIV-infected pregnant women were screened at 11 maternity health institutions in South Africa and were enrolled in an open-label short course ARV regimen of either nevirapine (Nvp) or multiple-dose zidovudine and lamivudine (Zdv/3TC). The overall estimated HIV-1 infection rates in 1307 infants by 8 weeks were 12.3% (95% confidence interval [CI], 9.7-15.0) for Nvp and 9.3% (95% CI, 7.0-11.6) for Zdv/3TC (P=.11). Excluding infections detected within 72 h (intrauterine), new HIV-1 infections were detected in 5.7% (95% CI, 3.7-7.8) and 3.6% (95% CI, 2.0-5.3) of infants in the Nvp and Zdv/3TC groups, respectively, in the 8 weeks after birth. There were no drug-related maternal or pediatric serious adverse events. Common complications were obstetrical for mothers (Nvp group, 24.3%; Zdv/3TC group, 26.3%) and respiratory for infants (Nvp group, 16.1%; Zdv/3TC group, 17.0%). This study further confirms the efficacy and safety of short-course ARV regimens in reducing MTCT rates in developing countries.

Adult↗
PubMed2003

Facilitating the WHO expanded program of immunization: the clinical profile of a combined diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine.

BACKGROUND: Vaccines are important weapons in the fight against infectious diseases. The World Health Organization (WHO) Expanded Program on Immunization (EPI) has been extended to include recommendations for hepatitis B and Haemophilus influenzae type b (Hib) vaccinations. The WHO has recommended that combined vaccines be used where possible, to reduce the logistic costs of vaccine delivery. This paper reviews the efficacy, safety and cost-effectiveness of Tritanrix-HB/Hib, the only commercially available combined diphtheria, tetanus, whole cell pertussis, hepatitis B and conjugated Hib vaccine. METHODS: The immunogenicity and reactogenicity results of five published clinical trials involving Tritanrix-HB/Hib in a variety of immunization schedules and countries were reviewed. Based on these data and cost-effectiveness studies, an assessment of its suitability for use in national immunization programs was made. RESULTS: Tritanrix-HB/Hib has shown excellent immunogenicity in clinical trials using a variety of schedules, with no reduced immunogenicity observed for any of the components of the combined vaccine. It has similar reactogenicity to DTPw vaccines alone. Pharmacoeconomic analyses have shown combined DTP-HB/Hib vaccines to be cost-effective compared to separate vaccines. CONCLUSIONS: Replacement of DTPw vaccination by Tritanrix-HB/Hib can be done without modifying the existing national immunization programs. This should facilitate widespread coverage of hepatitis B and Hib vaccinations and their rapid incorporation into the EPI.

Antibodies, Bacterial↗
PubMedDate not supplied

Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis.

BACKGROUND: HIV contributes substantially to child mortality, but factors underlying these deaths are inadequately described. With individual data from seven randomised mother-to-child transmission (MTCT) intervention trials, we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors. METHODS: Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age; and late infection by a negative PCR test at or after 4 weeks of age, followed by a positive test. Mortality rate was expressed per 1000 child-years. We investigated the effect of maternal health, infant HIV infection, feeding practices, and age at acquisition of infection on mortality assessed with Cox proportional hazards models, and allowed for random effects for trials grouped geographically. FINDINGS: 378 (11%) of 3468 children died. By age 1 year, an estimated 35.2% infected and 4.9% uninfected children will have died; by 2 years of age, 52.5% and 7.6% will have died, respectively. Mortality varied by geographical region, and was associated with maternal death (adjusted odds ratio 2.27, 95% CI 1.62-3.19), CD4+ cell counts <200 per microL (1.91, 1.39-2.62), and infant HIV infection (8.16, 6.43-10.33). Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children. In infected children, mortality was significantly lower for those with late infection than those with early infection (0.52, 0.39-0.70). This effect was also seen in analyses of survival from the age at infection (0.74, 0.55-0.99). INTERPRETATION: These findings highlight the necessity for timely antiretroviral care, for support for HIV-infected women and children in developing countries, and for assessment of prophylactic programmes to prevent MTCT, including child mortality and infection averted.

Africa South of the Sahara↗